Produção Nacional
Revisado por pares
α-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Model
2010; Lippincott Williams & Wilkins; Volume: 183; Issue: 4 Linguagem: Inglês
10.1016/j.juro.2009.12.007
ISSN1527-3792
AutoresMatthew N. Simmons, V. S. Subramanian, Sébastien Crouzet, Georges‐Pascal Haber, José R. Colombo, Osamu Ukimura, Søren Neilsen, Inderbir S. Gill,
Tópico(s)Renal and related cancers
ResumoNo AccessJournal of UrologyInvestigative Urology1 Apr 2010α-Melanocyte Stimulating Hormone Analogue AP214 Protects Against Ischemia Induced Acute Kidney Injury in a Porcine Surgical Modelis corrected byErratum Matthew N. Simmons, Vairavan Subramanian, Sebastien Crouzet, Georges-Pascal Haber, Jose R. Colombo, Osamu Ukimura, Søren Neilsen, and Inderbir S. Gill Matthew N. SimmonsMatthew N. Simmons Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Vairavan SubramanianVairavan Subramanian Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Sebastien CrouzetSebastien Crouzet Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Georges-Pascal HaberGeorges-Pascal Haber Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author , Jose R. ColomboJose R. Colombo Department of Urology, Universidade de São Paulo, São Paulo, Brazil More articles by this author , Osamu UkimuraOsamu Ukimura Kyoto Prefectural University of Medicine, Kyoto, Japan More articles by this author , Søren NeilsenSøren Neilsen The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark Financial interest and/or other relationship with ActionPharma. More articles by this author , and Inderbir S. GillInderbir S. Gill University of Southern California Institute of Urology, University of Southern California, Los Angeles, California More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.12.007AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: α-Melanocyte stimulating hormone protects kidneys against ischemia and sepsis induced acute kidney injury in rodents. We examined the efficacy of α-melanocyte stimulating hormone analogue AP214 to protect against acute kidney injury in higher vertebrates. Materials and Methods: We performed a prospective, blinded, randomized, placebo controlled study in 26 pigs. Laparoscopic technique was used for left nephrectomy and to induce complete warm ischemia in the right kidney for 120 minutes. AP214 (200 μg/kg intravenously) was administered daily on the day of surgery and for 5 days thereafter. Kidney function was measured for 9 days. We measured changes in serum creatinine, estimated glomerular filtration rate, serum C-reactive protein and urine interleukin-18. Results: In the placebo control and AP214 groups mean peak serum creatinine was 10.2 vs 3.92 mg/dl and the estimated glomerular filtration rate nadir was 22.9 vs 62.6 ml per minute per kg (each p = 0.001). Functional nadir occurred at 72 vs 24 hours in the control vs AP214 groups. Estimated glomerular filtration rate outcome on postoperative day 9 was 118 vs 156 ml per minute per kg in the control vs AP214 groups (p = 0.04). Conclusions: We noted a robust renoprotective effect of AP214. A similar AP214 effect may be observed in humans. Future research includes mechanistic studies in pigs and a phase II human clinical trial of AP214 in kidney transplant and partial nephrectomy populations. References 1 : Renal hypothermia: in vivo and ex vivo. Urol Clin North Am1983; 10: 637. Google Scholar 2 : The impact of warm ischaemia on renal function after laparoscopic partial nephrectomy. BJU Int2005; 95: 377. Google Scholar 3 : Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study. Lancet Oncol2006; 7: 735. Google Scholar 4 : Surgical renal ischemia: a contemporary overview. J Urol2008; 180: 19. Link, Google Scholar 5 : Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int2002; 62: 237. Google Scholar 6 : Apoptotic pathways in ischemic acute renal failure. Kidney Int2004; 66: 500. Google Scholar 7 : Cell cycle regulation: repair and regeneration in acute renal failure. Semin Nephrol2003; 23: 449. Google Scholar 8 : Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. J Clin Invest1997; 99: 1165. Google Scholar 9 : Unexpected abundance of HLA class II presented peptides in primary renal cell carcinomas. Clin Cancer Res2006; 12: 4163. Google Scholar 10 : Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev2004; 56: 1. Google Scholar 11 : Alpha-MSH production, receptors, and influence on neopterin in a human monocyte/macrophage cell line. J Leukoc Biol1996; 59: 248. Google Scholar 12 : Effect of bacterial endotoxin and interleukin-1 on prostaglandin biosynthesis by the hippocampus of mouse brain: role of interleukin-1 receptors and glucocorticoids. Neuroendocrinology1995; 62: 39. Google Scholar 13 : Pro-opiomelanocortin-derived peptides induce IL-10 production in human monocytes. J Immunol1996; 156: 2517. Google Scholar 14 : AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality. Kidney Int2008; 73: 1266. Google Scholar 15 : Serum creatinine can be used as a surrogate for glomerular filtration rate in single renal unit models. Can J Urol2009; 16: 4452. Google Scholar 16 : Alpha-melanocyte-stimulating hormone and related tripeptides: biochemistry, antiinflammatory and protective effects in vitro and in vivo, and future perspectives for the treatment of immune-mediated inflammatory diseases. Endocr Rev2008; 29: 581. Google Scholar 17 : Defining maximal renal tolerance to warm ischemia in porcine laparoscopic and open surgery model. Urology2005; 66: 1111. Google Scholar © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology20 May 2010Erratum Volume 183Issue 4April 2010Page: 1625-1629 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.KeywordsAP214kidneynephrectomynephrectomyischemiaAcknowledgmentsAction Pharma, Aarhus, Denmark, provided AP214.MetricsAuthor Information Matthew N. Simmons Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Vairavan Subramanian Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Sebastien Crouzet Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Georges-Pascal Haber Glickman Urologic and Kidney Institute, Cleveland Clinic Foundation, Cleveland, Ohio More articles by this author Jose R. Colombo Department of Urology, Universidade de São Paulo, São Paulo, Brazil More articles by this author Osamu Ukimura Kyoto Prefectural University of Medicine, Kyoto, Japan More articles by this author Søren Neilsen The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark Financial interest and/or other relationship with ActionPharma. More articles by this author Inderbir S. Gill University of Southern California Institute of Urology, University of Southern California, Los Angeles, California More articles by this author Expand All Advertisement PDF downloadLoading ...
Referência(s)